Der p 1-pulsed myeloid and plasmacytoid dendritic cells from house dust mite-sensitized allergic patients dysregulate the T cell response

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Abstract
Although reports suggest that dendritic cells (DC) are involved in the allergic reaction characterized by a T helper cell type 2 (Th2) profile, the role of myeloid (M‐DC) and plasmacytoid DC (P‐DC), controlling the balance Th1/Th2, remains unknown. Here, we showed that in Dermatophagoides pteronyssinus (Dpt)‐sensitized allergic patients and in healthy donors, M‐DC displayed a higher capacity to capture Der p 1, a major allergen of Dpt, than did P‐DC. However, Der p 1‐pulsed M‐DC from healthy subjects overexpressed CD80 and secreted interleukin (IL)‐10, whereas M‐DC from allergic patients did not. In contrast, with Der p 1‐pulsed P‐DC from both groups, no increase in human leukocyte antigen‐DR, CD80, and CD86 and no IL‐10 secretion were detected. When cocultured with allogeneic naive CD4+ T cells from healthy donors, Der p 1‐pulsed M‐DC from allergic patients favored a Th1 profile [interferon (IFN)‐γhigh/IL‐4low] and Der p 1‐pulsed P‐DC, a Th2 profile (IFN‐γlow/IL‐4high). In healthy donors, no T cell polarization (IFN‐γlow/IL‐4low) was induced by Der p 1‐pulsed M‐DC or P‐DC, but in response to Der p 1‐pulsed M‐DC, T cells secreted IL‐10. The neutralization of IL‐10 produced by Der p 1‐pulsed M‐DC from healthy donors led to an inhibition of IL‐10 production by T cells and a polarization toward a type 1. Thus, IL‐10 produced by M‐DC might be an essential mediator controlling the balance between tolerance and allergic status. In addition, P‐DC could contribute to the steady state in healthy donors or to the development of a Th2 response in allergic donors.
Funding Information
  • Aventis “GIP-HMR Fonds de Recherche”
  • University of Lille 2